Activation of murine macrophages. I. Different pattern of activation by poly I:C than by lymphokine or LPS.
The ability of poly I:C to activate mouse macrophages (M phi) to become tumoricidal was evaluated and compared with the ability of 2 other agents, lipopolysaccharide (LPS) and M phi-activating factor (MAF), to induce a tumoricidal state. All these agents were able to stimulate proteose-peptone-elicited M phi to kill RL male 1 tumor cells in an 18-hr 51Cr release cytotoxicity assay. High levels of cytotoxicity were obtained with concentrations as low as 1 microgram/ml of LPS or poly I:C and with 1/81 dilution of MAF. However, in the presence of reagents shown to contain less than 0.01 ng/ml of LPS by the LAL assay (LPS free), we found that poly I:C induced strong reactivity, whereas MAF was ineffective. The addition of 10 ng/ml of LPS during the stimulation period did not enhance the cytotoxicity induced by poly I:C, but it did restore MAF-induced, M phi-mediated cytotoxicity. In addition, poly I:C induced strong tumoricidal activity in resident M phi and in peritoneal exudate cells from the genetically defective C3H/HeJ mice that normally do not respond to LPS and MAF treatment. Therefore, it seems that although LPS is required as a second signal for MAF-induced cytotoxicity, such a second signal is not required for poly I:C-induced cytotoxicity. From the above results, it appears that poly I:C is a more powerful activating agent than LPS and MAF and either activates M phi via a different pathway or is effective on subpopulations of M phi that are not activated by the other agents.
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology*; D008223:Lymphoma / Q000276:immunology; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000276:immunology*; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010461:Peptones / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology*
D008070:Lipopolysaccharides; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D010461:Peptones; D011070:Poly I-C